Despite the fact that cognitive impairment affects more than 16 million people in the United States alone (CDC Cognitive Impairment, A Call to Action Now! 2011), there are very few, if any, diagnostic laboratory tests that can clearly indicate the presence, absence, or type of neurodegenerative disease, and diagnoses are generally based on clinical evaluations of symptoms that occur late in the development of the disease. Further complicating the issue, many neurodegenerative diseases have overlapping symptoms making them difficult to diagnose and treat appropriately.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which neurodegeneration starts decades before clinical symptoms appear (DeKosky S T, Marek K: “Looking Backward to Move Forward: Early Detection of Neurodegenerative Disorders,” Science (2003) 302 (5646): 830-834). It is the most common cause of dementia in the elderly, accounting for 50-60% of all cases (Blennow K, de Leon M J, Zetterberg H: “Alzheimer's Disease”: Lancet (2006); 368 (9533): 387-403) and it is believed that the number of people afflicted will reach over 100 million worldwide by 2050 (Ferri C P, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M et al, “Global Prevalence of Dementia: a Delphi Consensus Study”, Lancet (2005) 17; 366: 2112-7).
The symptoms of AD manifest slowly and the initial signs may only be mild forgetfulness. In this early stage, individuals have a tendency to forget recent events, activities, the names of familiar people or things and may not be able to solve simple mathematical problems.
As the disease progresses into moderate stages of AD, symptoms are more easily detected and become serious enough to cause people with AD or their family members to seek medical help. Moderate stage symptoms of AD include the inability to perform simple tasks such as grooming, and problems in speech, understanding, reading, and writing.
Severe stage AD patients may become anxious or aggressive, may wander away from home, and ultimately will need total care. While attempts have been made to create a diagnostic test using “multi-modal” methods combining the use of imaging techniques (e.g. PET scan, CT scan or MRI, for instance) with the detection of various biomarkers in cerebrospinal fluid (CSF) these methods are highly invasive, expensive, and have not been shown to be reliable in terms of sensitivity and specificity to detect AD accurately. The only definitive diagnostic currently available for AD is only employable post-mortem.
Parkinson's disease is a chronic, degenerative neurological disorder that affects one in 100 people over age 60. While the average age at onset is 60, some people are diagnosed at 40 or younger. Estimates of the number of people living with the disease vary, but recent research indicates that at least one million people in the United States, and more than five million people worldwide, have Parkinson's disease.
The cardinal symptoms of Parkinson's disease are resting tremor, bradykinesa and rigidity. To diagnose Parkinson's disease, doctors take a medical history and perform a thorough neurological examination. Doctors will also look for responsiveness to Parkinson's disease medications as further evidence that Parkinson's disease is the correct diagnosis. A DaTscan can be used to detect dopamine transporters in an individual suspected of having Parkinson's disease, but it is not a definitive test for Parkinson's disease. The lack of a definitive test for Parkinson's disease and the similarity of Parkinson's disease to other neurological conditions has led to a significant misdiagnosis rate with as many as 24% percent of cases being misdiagnosed (Rajput, 1991).
Despite advances in genomics in the last two decades, there is no objective test for Parkinson's disease, and Alzheimer's disease proteomics is still in its infancy. There is clearly an unmet need for diagnostic tests for neurological disorders such as Parkinson's and Alzheimer's disease.